Ginseng is an herb widely used by humans to treat lack of stamina, loss of appetite and cachexia, and impotence. In Asian medicine, ginseng is a common component in herbals used in treatment of cancer, including breast cancer. There is recent scientific evidence that ginseng and its ginsenoside components are effective in inhibiting breast cancer cell proliferation in vitro and tumor growth in vivo. Consequently, many patients may be taking ginseng supplements during treatment with standard chemotherapy and hormonal therapy regimens in an effort to enhance therapeutic results as well as ameliorate side effects of the cancer chemotherapeutic drugs. However, there is no information on how adjuvant ginseng use could influence the efficacy of the cancer therapeutic drugs. This R21 proposal will address the following questions. Will the adjuvant use of ginseng aid in or interfere with standard breast cancer chemo- or hormonal therapy? Will adjuvant ginseng use produce palliative effects in the breast cancer patient undergoing chemotherapy? To answer these questions, we will examine the effects of a wide dose-range of individual chemotherapy (doxorubicin, cyclophosphamide, paclitaxel) or hormonal (tamoxifen) therapy drugs, alone and in combinations with an extract of American ginseng, on the proliferation of human breast cancer cells (MCF-7, MDA-MB-231) in vitro. The results of this study will allow us to determine if adjuvant ginseng treatment alters the efficacy of standard cancer therapeutic drugs. From these results, we will determine the treatment regimens to be tested in vivo in female athymic nude mice inoculated with either MCF-7 or MDA-MB- 231 cells, monitoring tumor growth as well as general well-being and systemic toxicity. These preclinical studies will allow us to determine the potential palliative effects concomitant ginseng treatment may have in animals receiving the potent cancer therapeutic drugs. Thirdly, we will examine potential additive, synergistic or sub-additive effects of combination ginseng/chemotherapy treatment on pathway-specific genes/proteins involved in cell cycle regulation, apoptosis and cytotoxicity. Together, the results of these studies will provide us with a better understanding of American ginseng and will allow evidence-based decisions to be made by breast cancer patients and their physicians regarding complementary ginseng use during standard chemotherapy. [unreadable] [unreadable]